Major depressive disorder as a risk factor for suicidal ideation for attendees of educational institutions: a meta-analysis and meta-regression

Abstract Objective: This study aimed to analyze the effect of major depressive disorder (MDD) as a risk factor for suicidal ideation in individuals whose ages varied from 11 to 24 years and who were attending educational institutions. Data source: A systematic review was carried out by searching in PubMed and Biblioteca Virtual em Saúde (BVS). Original studies conducted in educational institutions, including individuals whose age varied from 11 to 24 years, in English, Spanish, or Portuguese were included. Data synthesis: Eight studies were selected for the meta-analysis, including 35,443 youths, with an average age of 16.8 years, predominantly female (51.2%), and from middle-income Asian countries (91.6%). An odds ratio of MDD of 3.89 (95%CI 2.46–6.17) for suicide ideation in youth was found. Subgroup analysis showed higher effects in Asia (OR=4.71; 95%CI 3.22–6.89) than Americas (OR=1.71; 95%CI 1.44–2.03). The meta-regression model indicated that younger adolescents (coef=-0.63; 95%CI 1.09–-0.18; p<0.01) and older studies (coef=-0.23; 95%CI 0.039–-0.08; p<0.01) presented higher effects of MDD on suicidal ideation. Conclusions: Early detection and treatment of MDD in youth patients are of utmost importance for preventing suicidal ideation. Educational institutions could play an important role in the early detection and intervention.


INTRODUCTION
Suicide is a complex and multifaceted phenomenon with a multifactorial etiology. There are many factors involved in suicidal behavior, including adverse experiences in early life, genetic and cultural characteristics, and traumatic experiences. 1 Suicidal ideation usually precedes suicide attempts and consummated suicide, encompasses characteristics such as self-destructive thoughts, and wishes plans possessed by individuals who have the purpose of ending their lives. 2 About 80% of the cases of suicide present a mental disorder, with major depressive disorder (MDD) being the most common. 3 Despite being a complex phenomenon, suicide can be prevented, especially with early interventions such as treatment and prevention of mental disorders, awareness of suicide and mental health, and limited access to means. 4 The vulnerability of adolescents for suicide behavior was shown in a study, 5 including individuals aged between 12 and 18 years, in which 19.8, 12.8, and 8.7% reported unstructured suicidal ideation, structured suicidal ideation, and attempted suicide at least once in the past 12 months, respectively.
MDD is considered a consistent predictor of suicidal behaviors in children and teenagers, as confirmed in multiple studies from different countries. In South Korea, Juon et al. 6 reported that among 10-21 years old students, those with severe MDD were 5.3 times more likely to report suicidal ideas and 3.2 times more likely to attempt suicide when compared to students with mild MDD. In both Hong Kongese (average age of 15.7 years old) and American (average age of 15.9 years old) students, MDD predisposed to suicidal ideation. 7 Self-injurious behaviors (SIBs) are common in adolescence. Brazil, for example, had an increase of 39.8% in the notifications from 2018 to 2019, and the age group from 15 to 19 years concentrated 23.3% of the cases. 1 There has been some debate about SIB being an independent diagnosis or a risk factor for a suicide attempt, ideation, or consummation. In 2016, a meta-analysis appointed SIB as a risk for later suicidal thoughts and behaviors. 8 The main purpose of this meta-analysis was to analyze the effect of MDD as a risk factor for suicidal ideation in individuals whose age varied from 11 to 24 years, who were attending educational institutions.

METHOD
The first step review of the literature included all original studies conducted in educational institutions (schools and colleges) with no restriction regarding the country of origin, including individuals whose age varied from 11 to 24 years, investigating MDD effects on suicidal ideation. Other studies aimed to investigate MDD as a risk factor for suicidal behaviors, suicide attempts, and consummated suicide, regardless of the age of the participants, were excluded, as well as studies in languages other than English, Spanish, and Portuguese, non-original articles.
The search was conducted in two electronic databases: PubMed database of the U.S. National Library of Medicine and BVS (initials in Portuguese that stand for "Biblioteca Virtual em Saúde"). The last search date was August 2020. We failed to find any similar ongoing meta-analysis in PROSPERO. Our systematic review protocol was registered on Open Science Framework with the following link: https://osf.io/sznpv.
In Pubmed, we employed the following Medical Subject Headings (MeSH), through the following search strategy: ((("Suicide"[Mesh]) AND "Risk Factors"[Mesh]) AND "Adolescent"[Mesh]) AND "Self-Injurious Behavior" [Mesh]. In BVS, we employed the following Health Science Descriptors (DeCS: initials in Portuguese that stands for Descritores em Ciência da Saúde), using the following search strategy: (tw:(suicídio)) AND (tw:(fatores de risco)) AND (tw:(adolescentes)) AND (tw:(automutilação)). In Scielo, we searched through DeCS, using the following search strategy: (suicídio) AND (fatores de risco) AND (adolescentes) AND (automutilação). In these searches, "self-injurious behavior" and automutilação were also considered synonyms of suicide attempts. Figure 1 shows the study selection, following the PRISMA statement. 9 The first and the last author conducted the selection process independently as the first step. We found 4,743 studies: 4,714 in PubMed, 29 in BVS. After excluding duplicates, 4,715 studies were considered primarily through titles and abstracts, and 4,341 studies did not meet the inclusion criteria. Afterward, the remaining 374 studies were fully read, and the other 366 were excluded for not meeting the inclusion criteria.
The first and last authors read all the eight studies included independently. Then, the first author tabulated the data. Then, the tabulated data were evaluated by the last author. In cases of discordance between the first and last authors on the information to be presented in the review, the penultimate author made the decision on the best way to report the data. The included articles were all evaluated by the JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data to address the possibility of bias.
This review reported information on the following variables: title of the study, author(s), year of publication, type of the study, sample size, methodology, sample characteristics (e.g., gender, average age, assessment scales, continents, and countries in which the studies were conducted), study design, outcome measures, and odds ratio (and 95%CI) for MDD as a risk factor for suicidal ideation. We included the logOR (and their 95%CI) of the eight studies in a meta-analysis model and used a random-effects model because a high heterogeneity was expected. The logOR was calculated since the log is necessary to calculate the confidence interval because of the asymmetrical nature of the OR scale 10 . I 2 has been calculated as a measure of between-study heterogeneity. Data were analyzed employing STATA software version 16. Then, we carried out a meta-regression model for gender, age, year of publication, and continents. Forest plots of the cumulative meta-analysis were derived for the first three continuous variables. Finally, we conducted a subgroup meta-analysis for the continent of the study, which was a categorical variable.

DISCUSSION
The present review gathered articles investigating MDD as a risk factor for suicidal ideation. Suicidal ideation is associated with an elevated risk for suicide attempts, representing an imminent risk of suicide, especially among adolescents. 19 The association between MDD and suicidal ideation is well known by any mental health professional. However, this was the first meta-analysis, to the best of our knowledge, reporting on the ORs for this association among adolescents in education institutions. We found a logOR of 1.36 in the present meta-analysis. These findings may be compared to a broader meta-analysis conducted by Guzmán et al. 20 investigating psychopathology-related variables predicting suicidal thoughts and behaviors. They found that the experience of suicidal thoughts and behaviors increased with the presence of general psychopathology. Mental disorders were well-known risk factors for suicide, being present in up to 90% of youths that commit suicide. [21][22][23] The incidence of suicidal ideation is higher among old than young adolescents. 24 In the U.S. National Comorbidity Survey, the incidence was lower than 1% and approximately 17% for those 10 and 18 years old, respectively. 24 However, our meta-regression showed an inverse pattern regarding age. We found that the younger the age of the individual, the greater the association between MDD and suicidal ideation. However, the lower mean age in the present meta-analysis was 13.1 years old.
Previous studies also found a relationship between gender, MDD, and suicidal ideation. 25,26 This finding was not supported by our study. The meta-regression did not show a significant relationship between gender and suicidal ideation.
In unfavorable socioeconomical contexts, adolescents show higher rates of suicidal attempts than those who live in a favorable socioeconomical context. 27,28 This evidence may lead countries with lower socioeconomic levels to take juvenile suicide as a priority in their public health policy. 29,30 In 2016, 80% of global suicides occurred in middle-and low-income countries, 31 with a relevant number of adolescents in their population. 32 Another study 33 has shown that one over five teenagers in low-income countries, aged 13-17 years, reported death thoughts, suicidal ideation, or had attempted suicide in the past 12 months (16.9, 17, and 17%, respectively). These prevalence rates were higher when compared to those of middleand high-income countries. Our meta-regression (Table 4) confirmed these findings, since the ORs found in Asia and North America were 0.55 (1.17-1.93) and 0.54 (0.37-0.71), respectively, with a tight correlation between MDD and suicidal ideation in low-and middle-income countries when compared to high-income ones. In our report (Tables 1-3), out of the eight selected studies, five 11,13,15,17,18 were conducted in middle-income countries (Taiwan, Vietnam, Malaysia, and Lebanon) and three 12,14,16 were conducted in high-income countries (the United States and South Korea).
Finally, we found a significant trend in the year of publication, with older studies reporting a higher association between MDD and suicidal ideation. This evidence might be explained considering the lack of policies, globally, regarding the children-youth mental health services and suicide prevention in the past decades. Recently, an increasing number of children and adolescent's mental health services, specific medical training, health promotion, and prevention policies have been promoted in many countries. 34,35 We opted to assess suicidal ideation attending educational institutions since suicide prevention strategies for this age group seem to be more effective in this setting when compared to traditional interventions, 36 as demonstrated by Wasserman et al. 37 Regarding the limitations of the study, the first is that our meta-analysis included studies conducted with students at school or college only. The second limitation includes that the answers provided by adolescents might have been affected by some cultural and social factors, including fear or shame, and provided in a socially expected manner. Finally, the third limitation includes the predominance of Asian and middle-income countries in the selected articles for this meta-analysis, which may influence the comparisons between middle-/low-income countries and high-income countries.

CONCLUSION
The present review found that MDD is a relevant risk factor for suicidal ideation among youths from 11 to 24 years old in educational institutions. In addition, younger age, older date of publication as well as the country of origin (Asian country) were associated factors with a tighter correlation between MDD and suicidal ideation. Thus, early detection of MDD and early interventions among adolescents are encouraged. Moreover, educational institutions may also play a relevant role in the early MDD detection programs. 38,39,40 Funding This study did not receive any funding.

Conflict of interests
The authors declare there is no conflict of interests.